GFRA4

GDNF family receptor alpha 4

Basic information

Region (hg38): 20:3659247-3663399

Links

ENSG00000125861 ∙ NCBI:64096 ∙ OMIM:618679 ∙ HGNC:13821 ∙ Uniprot:Q9GZZ7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GFRA4 gene.

• Inborn genetic diseases (17 variants)
• Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GFRA4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			14	4		18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	14	5	0

Variants in GFRA4

This is a list of pathogenic ClinVar variants found in the GFRA4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-3659928-G-A		not specified	Uncertain significance (Jul 12, 2022)
20-3660185-C-G		not specified	Likely benign (Feb 14, 2023)
20-3660517-G-C			Likely benign (Mar 29, 2018)
20-3660535-G-A		not specified	Uncertain significance (Jul 12, 2023)
20-3660648-G-T		not specified	Uncertain significance (Dec 01, 2022)
20-3660768-G-A		not specified	Uncertain significance (Jan 10, 2023)
20-3660799-A-G		not specified	Likely benign (Aug 02, 2023)
20-3660813-G-C		not specified	Uncertain significance (Jul 06, 2021)
20-3660920-G-T		not specified	Likely benign (May 11, 2022)
20-3660939-C-G		not specified	Uncertain significance (Feb 26, 2024)
20-3660990-A-G		not specified	Uncertain significance (Feb 27, 2024)
20-3661013-G-A		not specified	Uncertain significance (Nov 10, 2022)
20-3661053-C-T		not specified	Uncertain significance (Aug 08, 2023)
20-3661092-C-G		Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1	Uncertain significance (Jun 28, 2019)
20-3661107-G-A		not specified	Uncertain significance (Jul 26, 2022)
20-3661127-C-T		not specified	Uncertain significance (Jan 19, 2022)
20-3661136-G-C		not specified	Uncertain significance (Feb 28, 2023)
20-3661181-C-A		not specified	Uncertain significance (Mar 01, 2023)
20-3661208-C-G		not specified	Uncertain significance (Dec 15, 2022)
20-3661215-G-T		not specified	Uncertain significance (Dec 21, 2023)
20-3663377-G-A		not specified	Likely benign (Jun 27, 2022)
20-3663386-A-T		not specified	Uncertain significance (Apr 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GFRA4	protein_coding	protein_coding	ENST00000319242	5	4108

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00138	0.678	113528	0	2	113530	0.00000881

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.621	87	105	0.829	0.00000643	1760
Missense in Polyphen		15	16.174	0.92743		456
Synonymous	-0.568	52	47.0	1.11	0.00000289	689
Loss of Function	0.709	5	7.03	0.712	3.07e-7	105

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000103	0.000103
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for persephin. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor. May be important in C-cell development and, in the postnatal development of the adrenal medulla.
• Pathway: Developmental Biology;Signal Transduction;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;NCAM signaling for neurite out-growth;NCAM1 interactions;RET signaling;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.112

Haploinsufficiency Scores

• pHI: 0.0730
• hipred: N
• hipred_score: 0.180
• ghis: 0.529

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.255

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gfra4
• Phenotype: skeleton phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: MAPK cascade;nervous system development;axon guidance;negative regulation of ossification;glial cell-derived neurotrophic factor receptor signaling pathway
• Cellular component: extracellular space;plasma membrane;external side of plasma membrane;anchored component of membrane;receptor complex
• Molecular function: Ras guanyl-nucleotide exchange factor activity;glial cell-derived neurotrophic factor receptor activity